Embolotherapy is a minimally invasive or so-called "key-hole" surgical procedure in which an embolic or blocking agent is delivered through a catheter, into the targeted blood vessel, to inhibit or block blood flow to a tumor, or to minimize blood loss during surgery. The most common current embolic agents can be divided into four broad categories: sclerosants, mechanical occlusion devices, particulates and microspheres, and liquid embolic agents.

Sclerosants
::: Ethanol

Mechanical Devices
::: Coils
     :: Stainless
     :: Platinum
::: Balloons

Particles/Microspheres
::: PVA particles
::: Gelatin foam
::: Acrylic/gelatin coated microspheres

Liquids
::: nBCA
::: Ethylvinyl alcohol/DMSO solvent

Sclerosants (thickens or hardens tissues)

Absolute ethanol is the most commonly used sclerosing agent. Ethanol acts by denaturing proteins in the blood supply's microcirculation, resulting in the complete thrombosis (clotting) of the vessel. As a sclerosant, ethanol has a number of disadvantages. Firstly, it is extremely toxic. Secondly, it can easily flow beyond the targeted areas to be embolized, flow back, or flow to other areas, causing non-targeted embolization and/or necrosis of normal tissue. Thirdly, it is an extremely painful agent which requires the use of general anesthesia.

Ethanol has also been mixed with particulate embolic agents, e.g. PVA (poly vinyl alcohol) particles. In tumor embolization, ethanol as a cytotoxic agent facilitates tissue death. Other effective sclerosing agents include hypertonic saline, glucose solution and sodium tetradecyl sulphate.

Coils

Metallic coils are currently available in a wide variety of sizes and configurations. Coils are made of stainless steel or platinum, and most are coated with mylar filaments. Platinum microcoils are commonly used to treat aneurysms and arteriovenous malformations. Because of the ease of positioning microcoils, and their delivery by smaller catheters, they are particularly useful in procedures in the brain. Coil and particulate embolization are sometimes performed together to reduce the likelihood of symptoms recurring.

Balloons

Detachable balloons are available in a variety of shapes and sizes, in latex or silicone. Balloons have self-sealing valves and a high coefficient of expansion. These devices are effective in creating quick blockage of larger vessels. Detachable balloons have the advantage that they can be placed in an abnormal vessel and easily inflated, deflated, repositioned, removed or exchanged if its size or position is not ideal. Balloons deflate over time; usually, however, blood clotting around the balloon results in permanent blocking of the treated vessel despite balloon deflation.

Particles

The most common particulate agent currently in use is poly vinyl alcohol (PVA) particles. This product is provided in a range of sizes. The smaller particle sizes are most frequently used in the embolization (blockage) of large tumor masses, whereas larger sizes are most useful in the occlusion of larger, higher blood flow, vascular malformations.

A PVA particle embolization depends on the formation of a blood clot, in the target vessel to be blocked, around the PVA particles. Vessels embolized with PVA alone have a tendency to reopen after some weeks.

Other particulate agents include gelatin foam supplied as a powder and microfibullar collagen. Both are absorbable (break down over time) and do not provide permanent blockage of the vessel and, because of their small particle size, are associated with a high incidence of complications. This limits the use of both agents to very specific applications.

The gelatin foam is also available in sheets which can be cut into pieces called pledgets. These are often used to temporarily block and protect arteries further away from the target site from unwanted embolization when other more aggressive particulate or liquid embolic agents are being used.

Microspheres

A new embolic agent, acrylic microspheres coated with gelatin, has recently been introduced. The product is available in a wide range of diameters. Its blocking mechanism is similar to PVA particles and it is used primarily for the same indications: hypervascular tumors (large masses surrounded by a large network of blood vessels), arteriovenous malformations and the prevention of hemorrhaging during surgery.

The monodispersed, perfectly spherical, soft, elastic microspheres have several advantages over PVA particles, with their imprecise size and shape: clogging in the catheter is less likely to occur with microspheres; their use leads to more effective blockage of the blood supply and may reduce the possibility of blocking non-targeted vessels; the elastic properties of the microspheres can enable smaller catheters to be used.

Liquids

The most widely used liquid embolic agent is n-butyl-cyanoacrylate (nBCA). The agent instantly turns from a liquid to a gel (polymerizes) in contact with such substances such as blood, saline, ionic contrast media (used by the physician to view the procedure on an X-ray viewer called a fluoroscope). Currently, nBCA is the liquid embolic of choice for the majority of embolic procedures performed in the brain. Because of its flow characteristics, it allows easy injection via smaller catheters which can be placed in otherwise unreachable vessels. Its ability to rapidly stick to tissue adhesive leads to rapid blockage of high flow AVM's and a more permanent result than can be achieved with particulate agents.

There are, however, a number of serious disadvantages of nBCA. The catheter must be rapidly withdrawn after each injection of nBCA, resulting in frequent and time consuming catheter exchanges. Failure to withdraw the catheter increases the risk of gluing the catheter in place. For these reasons, nBCA is restricted to its important use in the treatment of aneurysms, AVM's and tumors in the brain for which there has been no alternative, effective liquid embolic agent.

A new liquid embolic agent has recently been introduced in Europe for aneurysms, neurovascular arteriovenous malformations and brain tumors. It is currently being clinically evaluated in the US. This liquid embolic agent consists of ethylvinyl-alcohol (EVA) copolymer dissolved in the solvent diethyl sulfoxide (DMSO). When introduced into the blood stream the DMSO disperses and the EVA separates out as a spongy mass. It forms a non-adhesive cast of the blood vessel network. Its non-adhesive properties are a clear advantage over nBCA. On the other hand, the possible toxicity of DMSO to the vessel wall is clearly a disadvantage of this agent.

It is clear there is a demand for non-adhesive flexible polymer embolic agents, which can be delivered in liquid form without the use of toxic solvents. BioCure's liquid embolic, LiquiGel™, currently in late stage development and due to be marketed in 2002, has been developed specially to provide a non-toxic, more efficient and permanent liquid/gel embolic system for embolotherapy.

These agents are delivered via a catheter, or long tube, which is most frequently inserted from the femoral artery after a small incision has been made in the groin of the patient. The catheter is then pushed along the blood vessel network until it reaches the desired site. In some neurovascular interventions, the catheter may be inserted into the jugular vein situated in the neck of the patient. As well as a blockage agent, embolic agents are also used to fill and seal aneurysms (an abnormal ballon-like bulging of the wall of an artery which may lead to rupture causing a large amount of blood loss or hemorrhagic stroke if untreated) and arteriovenous malformations – AVMs (mis-shapen blood vessels).

For more than 20 years, embolotherapy has been used by interventional radiologists to treat aneurysms, tumors, and to control blood loss during surgery. In recent years, interventional radiologists in the US, Europe and Japan have begun to expand the uses of embolotherapy. Increasingly embolotherapy and chemoembolotherapy are being used for the treatment of several different types of cancer tumors, including liver cancer. Embolotherapy is rapidly gaining acceptance and is being increasingly used to treat pelvic congestive syndrome, a leading causes of chronic pelvic pain in women. The use of embolotherapy is being explored in a number of other new indications.

A large variety of devices and materials have been tried for embolization: several are currently in use, some are under clinical investigation. There is, however, no single ideal embolic agent; and there is a demand for improved products.

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